These studies will investigate the relationship of thymic involution to the state of T-cell differentiation in peripheral lymphoid tissues. We shall test the hypothesis that as thymic function declines with age, the number of certain immature T cells increases. Immature T-cell populations will be identified by thier ability to form autologous rosetts (A-RFC), to bind peanut agglutinin (PNA+) and to express terminal deoxynucleotidyl transferase (TdT+) activity. We propose to quantiate the number of immature T cells in the central and peripheral organs of (a) normal adult mice, nude mice and animals thymectomized at birth or at 10 weeks of age, and (b) normal C57BL/6J and BALB/c mice of various ages. We will isolate A-RFC by A-rosetting and PNA+ cells by agglutination with the lectin, PNA. Using the fluorescence activated cell sorter (FACS), we will analyze and isolate cells having PNA receptors and those possessing TdT activity, using fluorescein-conjugated PNA and rhodamine-conjugated anti-TdT antibodies. We will define whether cells expressing these markers are representative of independent, overlapping or identical populations. Once isolated, we will study their functional markers (responses to mitogens, to allogeneic cells in MLR and syngeneic cells in SMLR). We will also analyze in vitro the effect of thymic hormones [thymopoietin, synthetic thymopoietin 32-36 (TP-5) and facteur thymique serque (FTS), thymosin-F5 and thymosin Alphaa, Beta3, Beta4] on the A-RFC, PNA+ and TdT+ cell populations. We will study in vivo the influence of TP-5 on those immature T-cell populations with aging. We postulate that cells of early T lineage will mature after exposure to thymic hormones. Finally, we will raise monoclonal antibodies to the specific antigenic determinants that characterize the lymphoid A-RFC and PNA+ cell populations. These studies will provide a better understanding of the immune status and immune potential that accompany aging and permit us to define and monitor the beneficial treatment of thymic hormones in aged mice.